GVHD Prophylaxis With Post Transplant Cyclophosphamide for Patients With Renal Insufficiency Undergoing a Conventional 8/8 HLA-matched Related or Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplant

• ClinicalTrials.gov Identifier: NCT02360111
• Recruitment Status: Terminated
• First Posted: February 10, 2015
• Results First Posted: November 8, 2018
• Last Update Posted: July 24, 2019
• Sponsor: Memorial Sloan Kettering Cancer Center
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Study Description

Brief Summary:

This is a pilot study which will be done in a small number of patients. The purpose of this study is to test the safety and benefit of giving a type of chemotherapy - cyclophosphamide - after the transplant to prevent graft versus host disease (GVHD) in patients with abnormal kidney function. GVHD is one of the most common complications of a stem cell transplant .

Condition or disease	Intervention/treatment	Phase
Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma	Drug: Cyclophosphamide	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Trial of GVHD Prophylaxis With Post Transplant Cyclophosphamide for Patients With Renal Insufficiency Undergoing a Conventional 8/8 HLA-matched Related or Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplant
• Actual Study Start Date: February 2015
• Actual Primary Completion Date: September 2017
• Actual Study Completion Date: September 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Post Transplant Cyclophosphamide; Melphalan 70 mg/m 2/d will be administered intravenously on d-6 and -5 Fludarabine 25 mg/m 2/d will be administered intravenously on d-6 thru -2 Day -1 will be a day or rest Cyclophosphamide and mesna will be given on d+3 and +4 Siro +/- MMF will be started in those patients who are to receive it on d+5. Neupogen will begin d+7.	Drug: Cyclophosphamide

Outcome Measures

Primary Outcome Measures :

1. # GVHD (Grade II-IV) Chronic GVHD Will be Diagnosed and Graded According to the (NIH Criteria) [ Time Frame: 2 years ]
   Chronic GVHD will be diagnosed and graded according to the (NIH criteria) treated with standard or experimental immunosuppressive therapy.

Secondary Outcome Measures :

1. Disease-free Survival [ Time Frame: 2 years ]
   DFS is defined as the minimum interval of time to relapse/recurrence, to death or to the last follow-up, from the time of transplant
2. Overall Survival [ Time Frame: 2 years ]
   Overall survival is defined as time from transplant to death or last follow-up.
3. # Renal Insufficiency Defined as a Calculated eGFR <60 ml/Min/1.73m2. Those With a eGFR < 30 ml/Min/1.73m2 Will be Considered Ineligible. [ Time Frame: 2 years ]
   Renal insufficiency is defined as a calculated eGFR <60 ml/min/1.73m2. Those with a eGFR < 30 ml/min/1.73m2 will be considered ineligible.
4. The Occurrence of Life-threatening Opportunistic Infections [ Time Frame: 2 years ]
   will be evaluated according to the criteria established by BMT CTN , and will be correlated with the level of immune recovery.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Age: Patients over age 18 who are deemed eligible for transplant by their treating physician.

• Disease status:

  1. AML in ≥ 1st remission - excluding those in 1st remission with 'good risk' cytogenetic features (i.e. t(8;21), t(15;17), inv 16).
  2. Secondary AML
  3. ALL/LL in 1st remission with clinical or molecular features indicating a high risk for relapse; or ALL > 2nd remission
  4. CML failing to respond to, progressing on or not tolerating appropriate TKI therapy in first chronic phase of disease; CML in accelerated phase, second chronic phase, or in CR after accelerated phase or blast crisis.

  5. Non-Hodgkins lymphoma with chemoresponsive disease in any of the following categories:

     1. high grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants or transplants requiring the use of calcineurin inhibitors.
     2. any NHL with therapy responsive disease which is considered not curable outside the transplant setting and not eligible/appropriate for autologous transplant or a higher priority protocol.
  6. Myelodysplastic syndrome (MDS): RA/RCMD with high risk cytogenetic features or transfusion dependence, RAEB-1 and RAEB-2 and AML evolved from MDS, who are not eligible for a higher priority protocol.

  7. Chronic myelomonocytic leukemia: CMML-1 and CMML-2, advanced polycythemia vera, and myelofibrosis.

     1. Patients must have a healthy HLA compatible (8/8 molecularly matched related, or unrelated) donor willing to undergo BM harvesting or PBSC apheresis after G-CSF administration. BM will be the preferred graft source.
     2. Patients diagnosed with any form of acute leukemia must have received induction and at least one course of consolidation chemotherapy pretransplant
• Patients must have a Karnofsky Performance Status > 70%

• Patients will have a eGFR <60 ml/min/1.73 m2

  1. Patients must have adequate organ function measured by: Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50% and must improve with exercise.
  2. Hepatic: ALT < 3 x ULN and total serum bilirubin < 1.5 x ULN, unless there is congenital benign hyperbilirubinemia
  3. Renal: eGFR > 30 ml/min/1.73 m2
  4. Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)
• Each patient must be willing to participate as a research subject and must sign an informed consent form.
• Patient must have a fully matched related or unrelated donor willing to donate stem cells.

Exclusion Criteria:

• Major surgery or irradiation within two weeks.
• Active CNS or extramedullary malignant disease.
• Active and uncontrolled infection at time of transplantation including active infection with Aspergillus or other mold, or HIV infection
• Pregnant or lactating women - they are excluded, given the potential teratogenic effects of chemotherapy and agents used in the transplant.
• Male and female patients of child-bearing potential unwilling to use effective means of contraception
• HIV or HTLV I/II positive, hepatitis C or chronic active hepatitis B.
• Patients who have had a previous malignancy unless they are deemed by their treating physicians to be at low risk for recurrence.
• Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up and research tests.

Contacts and Locations

Locations

United States, New York

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Ann Jakubowski, Ph.D., M.D.; Memorial Sloan Kettering Cancer Center

  Study Documents (Full-Text)

Documents provided by Memorial Sloan Kettering Cancer Center:

Study Protocol and Statistical Analysis Plan  [PDF] April 25, 2017

More Information

Additional Information:

Memorial Sloan Kettering Cancer Center 

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT02360111
• Other Study ID Numbers: 14-273
• First Posted: February 10, 2015
• Results First Posted: November 8, 2018
• Last Update Posted: July 24, 2019
• Last Verified: July 2019

Keywords provided by Memorial Sloan Kettering Cancer Center:

GVHD Prophylaxis; Cyclophosphamide; Renal Insufficiency; Hematopoietic Stem Cell Transplant; 14-273

Additional relevant MeSH terms:

Renal Insufficiency; Myelodysplastic Syndromes; Bone Marrow Diseases; Hematologic Diseases; Kidney Diseases; Urologic Diseases; Cyclophosphamide; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists