Clinical Trials for Rare Diseases

Below, we take a look at ongoing clinical trials for rare diseases. In addition to searching for new therapeutic targets and developing novel drugs for rare conditions, many researchers are investigating combinations of currently available therapies to treat diseases for which there are no or limited therapeutic options.

Bone Marrow Failure Diseases

A Multicenter, Open-Label, Pilot Study of Alisertib (MLN8237), a Novel Inhibitor of Aurora Kinase A, in Adult Patients With Relapsed/Refractory Acute Megakaryoblastic Leukemia or Myelofibrosis (Including Primary and Post-Essential/Post-Polycythemic Myelofibrosis) (NCT02530619)

  • study design: Multicenter, open-label, pilot safety/efficacy study
  • study start date: October 2015
  • estimated study completion date: July 2017
  • study status: Currently recruiting participants
  • estimated enrollment: 24
  • sponsor: Northwestern University

This study will evaluate the efficacy and safety of the investigational drug alisertib in patients with acute megakaryoblastic leukemia (AMKL) or myelofibrosis (MF). Alisertib has been shown preclinically to have an effect on megakaryocytes, which produce platelets and is known to be defective in both AMKL and MF.

Ruxolitinib Versus Best Available Therapy in Patients With High-risk Polycythemia Vera or High-risk Essential Thrombocythemia – The Ruxo-BEAT Trial (NCT02577926)

  • study design: Randomized, parallel-group, open-label safety/efficacy study
  • study start date: October 2015
  • estimated study completion date: December 2020
  • study status: Currently recruiting participants
  • estimated enrollment: 380
  • sponsor: RWTH Aachen University

Ruxolitinib is a JAK1/2-specific tyrosine kinase inhibitor that has been approved for the treatment of symptomatic MF and polycythemia vera (PV) in those who have had an inadequate response to or are intolerant of hydroxyurea. Ruxolitinib is being studied in phase II/III clinical trials for high-risk hydroxyurea-resistant or -intolerant PV and essential thrombocythemnia (ET). This study will assess the feasibility, efficacy, and safety of ruxolitinib treatment compared with best available treatment in patients with high-risk PV or ET.

Polycythemia Vera, Myelofibrosis and Essential Thrombocythemia: Identification of PV, MF & ET Genes (NCT00715247)

  • study design:  Observational, case-controlled, prospective study
  • study start date: July 2006
  • estimated study completion date: July 2020
  • study status: Currently recruiting participants
  • estimated enrollment: 700
  • sponsor: University of Utah

Researchers are hoping to identify genes whose mutations cause these myeloproliferative disorders. Finding these genes would aid in developing better diagnostic measures for these diseases and new therapies.

Extended Dosing With Eltrombopag in Refractory Severe Aplastic Anemia (NCT01891994)

  • study design: Open-label efficacy study
  • study start date: June 2013
  • estimated study completion date: May 2020
  • study status: Currently recruiting participants
  • estimated enrollment: 60
  • sponsor: National Heart, Lung, and Blood Institute

Severe aplastic anemia (SAA) is a life-threatening blood disease that can be successfully treated with immunosuppressive drug regimens or allogeneic hematopoietic cell transplantation (HCT). However, 20 to 40 percent of patients are ineligible for transplant due to the lack of an appropriate donor, age, or comorbidities. Eltrombopag, a second generation oral small molecule TPO-agonist, is being investigated for the treatment of SAA because it has been shown to increase platelets in healthy patients and thrombocytopenic patients.

A Two-Arm Phase II Clinical Study of the Clinical Efficacy and Safety of Tosedostat in Patients With Myelodysplastic Syndromes (MDS) After Failure of Hypomethylating Agent-Based Therapy (NCT02452346)

  • study design: Non-randomized, open-label, single-group assignment safety/efficacy study
  • study start date: February 2015
  • estimated study completion date: September 2018
  • study status: Currently recruiting participants
  • estimated enrollment: 80
  • sponsor: Weill Medical College of Cornell University

Tosedostat, an oral inhibitor of aminopeptidase that influences cellular protein clearance, has demonstrated activity in relapsed/refractory acute myeloid leukemia. This investigator-sponsored study will examine its efficacy in myelodysplastic syndromes.

Controlled Study of Rigosertib Versus Physician’s Choice of Treatment in MDS Patients After Failure of an HMA (INSPIRE) (NCT02562443)

  • study design: Randomized, parallel-assignment, open-label safety/efficacy study
  • study start date: October 2015
  • estimated study completion date: September 2018
  • study status: Currently recruiting participants
  • estimated enrollment: 225
  • sponsor: Onconova Therapeutics, Inc.

Patients with myelodysplastic syndromes (MDS) for whom the hypomethylating agents (HMA) azacitidine or decitabine have a poor prognosis have limited treatment options. In a previous study, ONTIME, the multikinase inhibitor rigosertib did not improve survival, compared with conventional care, for patients with MDS for whom the HMAs azacitidine or decitabine fail. However, patients who were primary-refractory to HMAs seemed to fare better. The INSPIRE study has a similar design to the ONTIME trial, but it enriches for higher-risk patients with no or transient responses to HMAs.

Clotting and Bleeding Disorders

A Phase 2, Open Label, Randomized, Dose Ranging, Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Study of AG-348 in Adult Patients With Pyruvate Kinase Deficiency (NCT02476916)

  • study design: Phase II, open-label, randomized, multicenter, dose-ranging safety/efficacy study
  • study start date: June 2015
  • estimated study completion date: March 2017
  • study status: Currently recruiting participants
  • estimated enrollment: 75
  • sponsor: Agios Pharmaceuticals, Inc.

The study will evaluate the safety and tolerability of multiple doses of AG-348, a novel, first-in-class, oral activator of the pyruvate kinase enzyme, as well as the drug’s pharmacokinetic (PK) and pharmacodynamic (PD) profile. Investigators also hope to identify early indicators of clinical efficacy. Adult patients with pyruvate kinase deficiency will receive multiple doses of AG-348 – for up to 24 weeks and for an extension period of up to two additional years.

A Phase III Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Prophylactic Emicizumab Versus No Prophylaxis in Hemophilia A Patients With Inhibitors (NCT02622321)

  • study design: Randomized, open-label, parallel assignment safety/efficacy study
  • study start date: November 2015
  • estimated study completion date: January 2018
  • study status: Currently recruiting participants
  • estimated enrollment: 70
  • sponsor: Hoffmann-La Roche

Emicizumab, or ACE910, the first-in-class factor VIIIa-mimetic bispecific antibody, was previously granted breakthrough therapy designation for the prophylactic treatment of patients with hemophilia A with factor VIII inhibitors. This multicenter study will further evaluate the safety, efficacy, and PK of prophylactic emicizumab in patients previously treated with episodic or prophylactic bypassing agents.

A Phase I Single-Ascending and Multiple-Ascending Dose, Safety, Tolerability, and Pharmacokinetics Study of Subcutaneously Administered ALN-AT3SC in Healthy Adult Volunteers and Hemophilia A or B Patients (Moderate or Severe Hemophilia) (NCT02035605)

  • study design: Randomized, single-blind, parallel assignment safety study
  • study start date: January 2014
  • estimated study completion date: April 2017
  • study status: Currently recruiting participants
  • estimated enrollment: 72
  • sponsor: Alnylam Pharmaceuticals

ALN-AT3SC works by reducing the liver’s production of the antithrombin protein, which plays a role in preventing blood from clotting. In previous animal research, ALN-AT3SC led to lower amounts of antithrombin protein in the blood; this first-in-human study will investigate whether single doses of ALN-AT3SC, administered subcutaneously, are safe in healthy volunteers and if multiple doses of ALN-AT3SC are safe in patients with hemophilia.


A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for CD25 Positive Hairy Cell Leukemia (NCT00321555)

  • study design: Open-label, phase II safety/efficacy study
  • study start date: April 2006
  • estimated study completion date: March 2019
  • study status: Currently recruiting participants
  • estimated enrollment: 27
  • sponsor: National Cancer Institute

Approximately 80 percent of patients with hairy cell leukemia (HCL) have malignant cells that express CD25 (Tac or IL2Ra). The experimental drug LMB-2 is a recombinant immunotoxin that has been shown to kill leukemia and lymphoma cells with the CD25 protein. The purpose of this study is to determine the activity of anti-Tac(Fv)-PE38 (LMB-2) in patients with CD25-expressing HCL. The study will assess response rate, response duration, LMB-2 immunogenicity, PK, toxicity, and monitor soluble Tac levels in the serum.

Randomized Phase II Trial of Rituximab With Either Pentostatin or Bendamustine for Multiply Relapsed or Refractory Hairy Cell Leukemia (NCT01059786)

  • study design: Randomized, crossover, open-label, phase II efficacy study
  • study start date: December 2009
  • estimated study completion date: December 2017
  • study status: Currently recruiting participants
  • estimated enrollment: 74
  • sponsor: National Cancer Institute

By combining rituximab with other anti-cancer drugs, investigators hope to improve outcomes for patients with hairy cell leukemia (HCL) whose disease has not responded well to or has recurred after standard therapies. This trial will help determine if pentostatin or bendamustine, when added to rituximab, could be a more effective treatment for HCL than rituximab alone.

A Phase III Study for Patients With Newly Diagnosed Acute Promyelocytic Leukemia (APL) Using Arsenic Trioxide and All-trans Retinoic Acid (NCT02339740)

  • study design: Open-label, phase III efficacy study
  • study start date: June 2015
  • estimated study completion date: April 2023
  • study status: Currently recruiting participants
  • estimated enrollment: 158
  • sponsor: Children’s Oncology Group

This study assesses treatment with tretinoin and arsenic trioxide in patients with newly diagnosed acute promyelocytic leukemia (APL). Standard treatment for APL involves high doses of anthracyclines, which are known to cause long-term side effects. Tretinoin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth, completely removing or reducing the need for anthracycline chemotherapy, which may reduce some of the long-term side effects.

Lymphoma & Myeloma

Phase 3 Multi-Center Randomized Study to Compare Efficacy and Safety of Romidepsin CHOP (Ro-CHOP) Versus CHOP in Patients With Previously Untreated Peripheral T-Cell Lymphoma (NCT01796002)

  • study design: Randomized, parallel-group, open-label, phase III safety/efficacy study
  • study start date: January 2013
  • estimated study completion date: July 2024
  • study status: Currently recruiting participants
  • estimated enrollment: 420
  • sponsor: The Lymphoma Academic Research Organisation

Although CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone) has limited efficacy in the setting of peripheral T-cell lymphoma (PTCL), it is widely used for the treatment of this disease. Trial investigators are evaluating whether adding the histone deacetylase inhibitor romidepsin to CHOP (Ro-CHOP) could improve its efficacy in patients with previously untreated PTCL.

Phase II Study of ABT-199 (GDC-199) In Patients With Relapsed Or Refractory Waldenström Macroglobulinemia (NCT02677324)

  • study design: Open-label, phase II safety/efficacy study
  • study start date: April 2016
  • estimated study completion date: February 2023
  • study status: Currently recruiting participants
  • estimated enrollment: 30
  • sponsor: Dana-Farber Cancer Institute

This study is assessing the safety and efficacy of ABT-199 – an oral agent that blocks BCL-2, a protein that is important for the survival of Waldenström macroglobulinemia cells – for patients with Waldenström macroglobulinemia who have relapsed after receiving at least one prior therapy or whose disease is refractory to treatment.